Elsevier

Neuroscience Letters

Volume 473, Issue 2, 5 April 2010, Pages 146-150
Neuroscience Letters

Delayed neural damage is induced by iNOS-expressing microglia in a brain injury model

https://doi.org/10.1016/j.neulet.2010.02.041Get rights and content

Abstract

Most CNS diseases begin with inflammation with subsequent neural damage eventually occurring; however, the process leading from the onset of inflammation to neural damage remains obscure. We used an artificial brain injury mouse model and examined how neural damage occurred in the brain parenchyma. The damaged area in each mouse was clearly observed by magnetic resonance imaging (MRI), and the progression of damage was observed to occur in a biphasic manner (acute damage, within 1 week; delayed damage, after 2 weeks). We found that the delayed neural damage was absent in iNOS-deficient mice (iNOS-KO mice). Then, we analyzed brain tissues and determined that delayed neural damage was accompanied by an increase in the levels of NO end products and iNOS expression, with accumulation of iNOS-expressing microglia around the injured area. In addition, the expression of IL-1β mRNA was increased in areas affected by acute damage, but not in those affected by delayed damage. These findings suggest that delayed neural damage might arise from NO production by iNOS-expressing activated microglia and that such activated microglia might become a therapeutic target for many CNS diseases.

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Acknowledgements

This study was supported by the Industrial Technology Research Grant Program from the New Energy and Industrial Technology Development Organization (NEDO) of Japan and the Hori Information Science Promotion Foundation.

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